In our prior U.S. Pat. No. 3,879,537 entitled "Treatment of Ichthyosiform Dermatoses" we described and claimed the use of certain alpha hydroxyacids, alpha ketoacids and related compounds for topical treatment of fish-scale like ichthyotic conditions in humans. In our U.S. Pat. No. 3,920,835 entitled "Treatment of Disturbed Keratinization" we described and claimed the use of these alpha hydroxyacids, alpha ketoacids and their derivatives for topical treatment of dandruff, acne, and palmar and plantar hyperkeratosis.
In our prior U.S. Pat. No. 4,105,783 entitled "Treatment of Dry Skin" we described and claimed the use of non-irritating compositions containing reaction products formed between an alpha hydroxyacid or alpha ketoacid and ammonium hydroxide or an organic primary, secondary or tertiary alkyl amine or the like having from 1 to 8 carbon atoms, for topical treatment of dry skin. In our recent U.S. Pat. No. 4,246,261 entitled "Additives Enhancing Topical Corticosteroid Action" we described and claimed that alpha hydroxyacids, alpha ketoacids and their derivatives could greatly enhance the therapeutic efficacy of corticosteroids in topical treatment of psoriasis, eczema, seborrheic dermatitis and other inflammatory skin conditions.
In our U.S. Pat. No. 4,363,815 entitled "Alpha Hydroxyacids, Alpha Ketoacids and Their Use in Treating Skin Conditions" we described and claimed that alpha hydroxyacids and alpha ketoacids related to or originating from amino acids, whether or not found in proteins, were effective in topical treatment of skin disorders associated with disturbed keratinization or inflammation. These skin disorders include dry skin, ichthyosis, palmar and plantar hyperkeratosis, dandruff, Darier's disease, lichen simplex chronicus, keratoses, acne, psoriasis, eczema, pruritus, warts and herpes.
In our recent U.S. patent application Ser. No. 945,680 filed Dec. 23, 1986 now abandoned and entitled "Additives Enhancing Topical Actions of Therapeutic Agents", we described among other things that incorporation of an alpha hydroxyacid or related compound can substantially enhance therapeutic actions of cosmetic and pharmaceutical agents. We also described methods of treating wrinkles and skin changes associated with aging using an alpha hydroxyacid or related compound.
In our more recent U.S. patent application Ser. No. 393,749 filed Aug. 15, 1989 and entitled "Amphoteric Compositions and Polymeric Forms of Alpha Hydroxyacids, and Their Therapeutic Use", now U.S. Pat. No. 5,091,171, we described among other things compositions containing an amphoteric complex formed between an alpha hydroxyacid or related compound and an amphoteric or pseudoamphoteric agent are therapeutically effective for topical treatment of various cosmetic conditions and dermatologic indications.
In our most recent U.S patent application Ser. No. 683,437 filed Apr. 10, 1991 and entitled "Compositions Comprising 2-Hydroxycarboxylic Acid and Related Compounds, and Methods for Alleviating Signs of Dermatologic Aging", now abandoned we described among other things that compositions containing an alpha hydroxyacid or related compound are therapeutically effective for topical treatment of dermatological signs of aging. The signs of aging include changes or damage to skin, nail and hair associated with intrinsic aging, as well as changes or damage caused by extrinsic factors such as sunlight, radiation, air pollution, wind, cold, heat, dampness, chemicals, smoke and cigarette smoking.
In recent U.S. Pat. No. 5,425,938 entitled "Polyamino Salts of Alpha-Hydroxyacids, Alpha-Ketoacids and Related Compounds" it is disclosed that such polyamino salts might be used in cosmetic compositions. The claimed amino polymers have optimal molecular weights of from 10,000 to 800,000. However, according to Jackson S. M., Elias P. M.: SKIN AS AN ORGAN OF PROTECTION cited in Fitzpatrick T. B., Eisen A. Z., Wolff K., Freedberg I. M., Austen K. F. (ed.): DERMATOLOGY IN GENERAL MEDICINE, 4th edition, McGraw-Hill, Inc., New York; 1993: Chapter 16, 241-253, experiments have shown that even non-polar polymers with molecular weight of above 800-1000 decrease dramatically in penetration through the stratum corneum of the skin. Therefore, such amino polymers cannot readily penetrate the stratum corneum of human skin due to their high molecular weight and polar nature of the polyamino salt.
Each of the foregoing patents and applications is expressly incorporated herein by reference in their entireties.
It has been established through scientific and clinical studies that alpha hydroxyacids and related acids are therapeutically effective for topical treatment of various cosmetic and dermatologic indications associated with disturbed keratinization and skin changes associated with aging. However, the compositions containing these acids may irritate human skin on repeated topical applications, due to lower pH of the formulations and uncontrolled release and penetration of the acids into stratum corneum of the skin. We have found, for example, that a product containing 12% lactic acid with pH 4.8 can still irritate sensitive skin or atopic skin if the composition is not formulated under controlled-release basis.